In this project, we will develop a novel imaging system that combines a high-field MRI scanner and an ultrahigh resolution SPECT system for imaging metabolic and signaling targets in the pancreatic beta cell. This combined system comprises a 9.4 T 30 cm horizontal bore magnet (Oxford Instrument, Oxford, UK) with Bruker Avance Biospec (Bruker-Biospin, Billerica, MA) console equipped with 12 cm shielded gradient with maximum strength of 400mT/m, and a compact and ultrahigh resolution SPECT system that will be fitted inside the 12 cm diameter bore to allow simultaneous MR and SPECT imaging of mouse. The proposed SPECT system is based on an energy-resolved photon counting detector. It consists of pixelated CdZnTe (CZT) crystals (with 350 5m W 350 5m pitch), coupled to a custom- designed readout circuitry that utilizes an energy-resolved photon-counting (ERPC) ASIC (developed by Dr. Meng's group at UI) to readout anode pixels and the NCI-ASIC (developed by Brookhaven National Laboratory and Naval Research Laboratory) to readout the cathode signals. The ERPC detector offers (a) an ultrahigh intrinsic spatial resolution (<400 5m in all three dimensions) for 140keV 3-rays, (b) a wide dynamic range to cover 12-200keV, (c) a proven MRI- compatibility with minimized magnetic components, (d) the ability to extract signals simultaneously induced on adjacent anode pixels and the cathode, which provides critical information for correcting the event positioning error induced by the strong magnetic field, and (e) a compact form factor for packing multiple detectors into the MRI bore. The proposed imaging system combines a high-field (9.4 T) MRI scanner with an ultrahigh SPECT system. It allows an excellent co-registration of the features resolved in both MR and SPECT images. The proposed system will be applied for imaging metabolic and signaling targets in the pancreatic beta cell. The results of studies will enhance our understanding of the advantages and limitations of each imaging modality in specific models of 2cell loss and replication. PUBLIC HEALTH RELEVANCE: Type 2 diabetes mellitus (T2DM) is one of the most important medical problems of our time, with a dramatically increasing incidence affecting over 20 million persons in the United States and accounting for over $200 billion/yr in total medical costs and lost wages. New methods to treat autoimmune Type 1 diabetes would also benefit from an assessment of b-cell mass/function to monitor immune attack and possible ongoing replication as well as the fate of transplanted islets or b-cells generated from stem or other progenitor cells [9-11]. Useful, validated techniques to remains a long sought after target. In this project, we will develop a combined SPECT/MRI system that is dedicated to imaging radiolabeled cells in small lab animals. This system would offer a unique instrument for non-invasively assess b-cell mass and function in mice. We expect also that the combination of the ultrahigh resolution SPECT system and high-field MRI system would make a substantial impact to many other areas, such as in vivo tracking of radiolabeled stem cells and T cells, as well as imaging tumors in small animals.